Clinical Inquiries

What is the most effective treatment for external genital warts?

French L, Nashelsky J, White D. J Fam Pract 2002 Apr;51(4):313.

Evidence-based Answer

Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. (Grade of recommendation: B, based on systematic review.) No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.

Evidence-based Summary

Nonsurgical treatments that are beneficial in eradicating genital warts are podofilox (Condylox) (8 randomized controlled trials [RCTs] with 1035 participants), imiquimod (Aldara) (2 RCTs with 968 participants), and intralesional interferon (8 RCTs). Cryotherapy is equivalent to trichloroacetic acid1,2 and electrosurgery.3 Although surgical treatments have not been compared with placebo or no treatment, both electrosurgery and surgical excision are superior to podophyllin in clinical trials.4,5 Laser surgery is as effective as surgical excision.6 Studies of topical interferon show conflicting results.7 Systemic interferon is not beneficial.7 Topical 5-FU has not been studied with RCTs. Wart clearance rates are summarized in the Table. Treatment duration for nonsurgical options is 4 to 8 weeks. Treatment of genital warts has not been shown to reduce transmission to sex partners.7

Two RCTs4,5 showed more frequent recurrence with podophyllin (60% to 65%) than with surgical excision (19% to 20%). Another trial1 showed recurrence in 22% of participants receiving electrosurgery, in 21% of those receiving cryotherapy, and in 44% of those receiving podophyllin treatment. Data are lacking on recurrence rates with imiquimod, podofilox, and intralesional interferon.

Pain occurs in less than 20% of people with imiquimod, cryotherapy, podophyllin, and electrosurgery; 39% with topical interferon; 44% with electrosurgery; 75% with podofilox; and 100% with surgical excision or laser surgery.7 However, pain has been measured using methods that are unlikely to be comparable across studies. Flulike symptoms, leukopenia, thrombocytopenia, and elevated aspartate transaminase levels are associated with intralesional interferon.7 Topical medications have not been studied in pregnant patients. Cryotherapy is safe in pregnancy based on case series, if only 3 or 4 treatments are given.7

Direct comparisons between home therapies (imiquimod, podofilox) and other treatments are needed. Products for home use are relatively expensive: a 1-month supply of imiquimod costs approximately $150; a 1-month supply of podofilox, $110 to $130. These are average wholesale prices, rounded to the nearest $10, as of Feb. 15, 2002.

Clinical Commentary

In practice, my experience has been that patients have various expectations with regard to any therapy for genital condyloma. Primary among these are clearing of lesions without recurrence at some later date, and elimination of risk of transmission of HPV to partners. This review, although helpful in providing relative efficacy of multiple therapies, does not directly address these outcomes, as length of follow-up in these studies is usually limited, and none address the issue of whether short or long-term transmissibility is affected.

A tip: While working in a state prison setting, where refractory warts were common, I found that topical application of bi-chloroacetic acid, although certainly more painful at the time of application than podophyllin or imiquimod, provided complete clearing of such lesions in nearly all cases. My impression is that recurrence rates were no worse with BCA than with other topical therapies.

Recommendations from Others

The CDC endorses podophyllin, bi- and trichloroacetic acid, podofilox, imiquimod, cryotherapy, intralesional interferon, electrosurgery, laser surgery, and surgical excision.8 A United Kingdom guideline on anogenital warts recommends physical ablative methods such as cryotherapy and surgical options for keratinized lesions and topical medications for soft lesions. The guideline also recommends ablative therapy for persons with a small number of warts regardless of type. Interferon and 5-FU are not recommended.9

Clinical Commentary by David White, MD, at http://www.fpin.org.

Figures

CLEARANCE RATES REPORTED IN CLINICAL TRIALS
Therapy Clearance Rate (%)
Cryotherapy 63–88
Electrosurgery 61–94
Imiquimod 37–56
Interferon (topical) 6–90
Interferon (intralesional) 17–63
Laser surgery 23–52
Podofilox 45–77
Podophyllin 32–79
Surgical excision 35–72
Trichloroacetic acid 50–81
Placebo or no treatment 0–56

References

  1. Abdullah AN, Walzman M, Wade Anull 1993. Volume 20. Page(s): 344-5.
  2. Godley MJ, Bradbeer CS, Gellan M, Thin RNnull 1987. Volume 63. Page(s): 390-2.
  3. Stone KM, Becker TM, Hadgu A, Kraus SJnull 1990. Volume 66. Page(s): 16-9.
  4. Khawaja HTnull 1990. Volume 35. Page(s): 1019-22.
  5. Jensen SLnull 1985. Volume 2. Page(s): 1146-8.
  6. Duus BR, Philipsen T, Christensen JDet al. 1985. Volume 61. Page(s): 59-61.
  7. Wiley DJnull Genital warts. December 2000. Page(s): 910-8. Clin Evidence Issue 4,.
  8. No author listed. Centers for Disease Control and Prevention. 1998. Volume 47(RR-1). Page(s): 91-4.
  9. No author listed. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). 1999. Volume 75(suppl 1). Page(s): 71-5S.